IE851229L - Pharmaceutical compositions - Google Patents
Pharmaceutical compositionsInfo
- Publication number
- IE851229L IE851229L IE851229A IE122985A IE851229L IE 851229 L IE851229 L IE 851229L IE 851229 A IE851229 A IE 851229A IE 122985 A IE122985 A IE 122985A IE 851229 L IE851229 L IE 851229L
- Authority
- IE
- Ireland
- Prior art keywords
- pharmaceutical composition
- active ingredient
- salt
- methyl
- composition according
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N Minaline Natural products OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 230000001506 immunosuppresive effect Effects 0.000 claims abstract description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- -1 ferrous metals Chemical class 0.000 description 8
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 6
- 229960002170 azathioprine Drugs 0.000 description 6
- 239000003826 tablet Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- 206010036030 Polyarthritis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 208000030428 polyarticular arthritis Diseases 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000009109 curative therapy Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- 229940116731 Uricosuric agent Drugs 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001399 anti-metabolic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000043 immunodepressive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003383 uricosuric agent Substances 0.000 description 1
- 230000003424 uricosuric effect Effects 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
This invention relates to novel pharmaceutical compositions having immuno-suppressive activities, the active ingredient of which is a 4-aroyl N-alkyl or aryl pyrrolyl-2 carboxylic acid or a salt thereof. The pharmaceutical compositions have therapeutic utility for treating auto-immune diseases, or in the prevention of rejection of graft organs.
Description
12 IRELAND PATENTS ACT. 1964 COMPLETE SPECIFICATION "Pharmaceutical compositions having immuno-suppressive properties" Patent Application by ALBERT ROLLAND S.A., Societe Anomyne organised and existing under the laws of France of 49, Rue St-Andre-des Arts, 75006 Paris, France. «» ri it i) 4 - 1 - This invention relates to derivatives of N-methyl pyrolle carboxylic acid.
More precisely, it relates to aroylated derivatives of N-alkyl pyrrole carboxylic acids. 5 Specifically the subject matter of this invention provides pharmaceutical compositions endowed with immuno suppressive properties containing as active ingredient at least one 4-aroyl pyrrolyl-2carboxylic acid derivative of the general formula I wherein Ar is a member selected from the group consisting of phenyl, halogenophenyl, naphtyl-1 and naphtyl-2 and R1 is methyl or phenyl in conjunction or admixture with an inert non toxic pharmaceutically-compatible carrier or vehicle. - 2 - Similarly the active ingredient may also be an addition salt of a compound of formula I with a pharmaceutically acceptable mineral or organic base.
Some pyrrolyl-2 carboxylic acids are already known having been 5 previously disclosed in the US patent 2,479,972 as possessing local anaesthetizing properties. Other pyrrolyl alkanoic acids, namely 5-aroyl pyrrolyl alkanoic acids have already been disclosed in the US patent 3,865,840. They can be used as anti-inflammatory agents. Moreover the derivatives of 10 pyrrolyl carboxylic acids having the general formula COOR, have been already disclosed in the French patent 2,405,246. They are endowad with uricosuric properties, or at least, they increase the rate of elimination of a colouring matter Phenol 15 Red in the rats as did the known uricosuric agents.
The present invention substantially resides in the fact that some compounds disclosed in the French patent 2,405,246 and other related compounds which are not within the scope of the - 3 - said French patent, evidence new properties of the immuno-depressive type.
The immuno-suppressive properties may be evidenced by the inhibition of the formation of rosettes shown after having 5 contacted spleen cells of mice C57 BL5 with heterologous red blood cells of sheep. The inhibition is shown "in vitro" using concentrations of active compound of formula I ranging from 5 to 50 jj.g/ml.
As an example N-methyl 4-(naphtoyl-2) pyrrolyl-2 carboxylic 10 acid is about as active as the known antimetabolic substance Azathioprine, taken as reference substance (IC^ = 6 jig/ml). In contrast to Azathioprine, the compounds of formula I are of reduced toxicity and particularly devoid of any toxicity on the blood cells. 15 The pharmaceutical compositions according to the invention are useful for treating or alleviating the auto-immune diseases, such as erythematous lupus, rheumatoid polyarthritis, multiple sclerosis and also for preventing the rejection of graft tissues. 20 Generally speaking these pharmaceutical compositions according to the invention, contain from 25 to 1000 mg of active ingredient per unit dosage and preferably from 50 to 500 mg per unit dosage. - 4 - The immuno-suppressive pharmaceutical compositions according to the invention are those intended for administration by oral, parenteral, rectal, permucous or percutaneous way of administration. For these purposes the pharmaceutical 5 compositions will be in the form of uncoated or coated tablets, dragees, pills, capsules, soft gelatine capsules, drops, drinkable solutions or suspensions, suppositories, injectable solutions or suspensions or solutions in a polar medium for percutaneous applications. 10 The daily dosages may vary considerably depending on the nature of the auto-immune disease to be treated, on the age of the disease and the organic or articulary damages this disease has already caused. Preferably the daily dosage will range from 25. to 2000 mg of active ingredient in the man. 15 Among the compounds of formula I the most preferred ones are: 4-(2-bromobenzoyl) N-methylpyrrolyl-2 carboxylic acid 4-(naphtoyl-1 ) N-methyl pyrrolyl-2 carboxylic acid 4-(naphtoyl-2) N-methyl pyrrolyl-2 carboxylic acid.
In the foregoing, the base addition,salts of the compounds of 20 formula I are defined as the salts of an alkali metal base such as sodium, potassium, lithium, ammonium or rubidium; the salts of the earth-alkali metal base such as calcium or strontium; magnesium, aluminium or the ferrous metals. Here - 5 - may also be included the alkylamine salts, the cyclo alkylamine salts, the aryl lower alkylamines salts, the pyridyl lower alkylamines salts, the furyl lower alkylamines salts, the hydroxy lower alkylamines salts, the aminoacids 5 salts, the deso-xyhexose or pentosamines salts, the aminohexitols or pentitols salts, the substituted guanidine salts, the polypeptides salts, and similar basic compounds.
The compounds of formula I are produced according to the process disclosed in the French patent 2,405,246 or by an 10 equivalent process.
The following examples are merely intended to illustrate the invention without limiting it in any manner.
EXAMPLE 1 Tablets having 250 mg of 4-(Naphtoyl-2) N-methyl pyrrolvl-2 15 carboxylic acid 4-(Naphtoyl-2) N-methyl pyrrolyl-2 carboxylic acid 250 g Wheat starch 180 g Maize starch 20 g Colloidal silica 10 g 20 Polymer of ethylene glycol and propylene glycol sold under the Trade Mark Pluronic F 68 25 g Magnesium stearate 40 g Ethyl cellulose 20 g Talc 15 g - 6 - For 1000 tablets having a mean weight of .560 g EXAMPLE II Tablets having 300 mg of 4-(Naphtovl-1) N-methvl pyrrolyl-2 carboxylic acid 4-(Naphtoyl-1) N-methyl pyrrolyl-2 carboxylic acid 300 g Magnesium phosphate 150 g Calcium sulphate 60 g Arabic gum 15 g Talc 35 g 10 For 1000 tablets having a mean weight of .55 g.
EXAMPLE III Soft gelatine capsules having 250 mg of 4-(2-bromobenzoyl) trine thy 1 pyrrolyl-2 carboxylic acid per unit dosage 4-(2-bromobenzoyl) N-methyl pyrrolyl-2 carboxylic acid 250 g 15 Lactose 125 g Mannitol 10 g Talc 12 g Magnesium stearate 13 g For 1000 soft gelatine capsules having a mean weight of .290 20 g.
EXAMPLE IV Pharmacological study on the immuno-suppressive properties of the compounds of formula I The immuno-suppressive properties have been evidenced on pharmacological tests, namely on models of auto-immune diseases in the rat: polyarthritis after Freund's adjuvant in curative or preventive therapy Allergic encephalitis in the Lewis rat.
The pharmaceutical compositions according to the invention have good effectivity in the polyarthritis after Freund's adjuvant from a daily dosage corresponding to 200 mg/kg orally when administered to the steady state of the disease (from the 21st to the 35th day after injection of the Freund's adjuvant) i.e. in curative therapy - Using the same experimental conditions Azathioprine is inactive.
When the daily therapy is initiated as a preventive drug from the last day before the injection of Freud's adjuvant, the pharmaceutical compositions according to the invention are effective from a dosage corresponding to 100 mg/kg of active ingredient daily orally. In similar experimental conditions Azathioprine is effective from a dosage of 20 mg/kg. - 8 - Furthermore the pharmaceutical compositions according to the invention protect the rats against allergic encephalomyelitis: - at a dose of 100 mg/kg of active ingredient for two days: 50% protection 5 - at a dose of 400 mg/kg of active ingredient : 90% protection - at a dose of 100 mg/kg Azathioprine affords a protection of 90%.
The pharmaceutical compositions according to the invention even when administered at a dose of 400 mg/kg daily for 30 10 days do not alter the white blood cells and the red blood cells counts whilst Azathioprine from a dose of 20 mg/kg for the same time, causes a marked decrease of the blood cells. - 9 -
Claims (11)
1. . The pharmaceutical compositions having immuno-suppressive action containing as active ingredient at least one compound of formula I (1) coon wherein Ar is a member selected from the group consisting of a phenyl, a halogenophenyl radical, a naphthyl-1 and a naphtyl-2 radical R-, is a methyl or a phenyl radical 10 in admixture or conjunction with an inert non toxic pharmaceutically-acceptable vehicle or carrier.
2. A pharmaceutical composition according to claim 1 in which the active ingredient is a mineral or organic base addition salt of a compound of formula I. 15
3. A pharmaceutical composition according to any of claims 1 or 2 wherein the amount of active ingredient ranges from 2.5 to 1000 mg per unit dosage. - 10 -
4. A pharmaceutical composition according to any of claims 1 or 2, wherein the carrier or vehicle is one of those suitable for oral or parenteral administration.
5. A pharmaceutical composition according to Claim 1 or 2 5 wherein the active ingredient is 4-(Naphtoyl-1) N-methyl (pyrrolyl-2) carboxylic acid or a salt thereof with an inorganic or organic base.
6. A pharmaceutical composition according to any of claims 1 to 2 wherein the active ingredient is 4-(Naphtoyl-2) N- 10 methyl pyrrolyl-2 carboxylic acid or a salt thereof with an organic or inorganic base.
7. A pharmaceutical composition according to any of claims 1 to 2 wherein the active ingredient is 4-(2-bromobenzoyl) N-methyl pyrrolyl-2 carboxylic acid or a salt thereof with a 15 mineral or organic base.
8. A process for producing a pharmaceutical composition with immuno-suppressive action according to claim 1 which consists in mixing or adjuncting at least one compound of formula I, (I) Ar - C 0 coon M R 1 - 11 - wherein Ar and R1 have the above-given definitions, or a salt thereof with an organic or inorganic base together with an inert non-toxic, pharmaceutically-acceptable vehicle or carrier. 5
9. A compound of the formula (I) COOH wherein Ar is phenyl, a halogenophenyl Radical, a naphtyl-1 or a naphthyl-2 radical, and R1 is a methyl or phenyl radical or a pharmaceutically acceptable salt thereof, for use in the 10 manufacture of a composition for application in the treatment or prophylaxis of an auto-immune disease.
10. A pharmaceutical composition substantially as hereinbefore described with reference to the Examples. - 12 -
11. A process substantially as hereinbefore described with reference to the Examples. Dated this 17th Day of May 1985, CRUICKSHANK & CO., For and on behalf of the Applicants, 1 Holies Street, Dublin 2.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8408200A FR2564831B3 (en) | 1984-05-25 | 1984-05-25 | NOVEL DERIVATIVES OF AROYL- OR HYDROAROYL N-ALCOYL PYRROLYL-2 CARBOXYLIC ACIDS AND NEW IMMUNO-SUPPRESSIVE PHARMACEUTICAL COMPOSITIONS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE851229L true IE851229L (en) | 1985-11-25 |
| IE57994B1 IE57994B1 (en) | 1993-06-02 |
Family
ID=9304387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1229/85A IE57994B1 (en) | 1984-05-25 | 1985-05-17 | Pharmaceutical compositions having immuno-suppressive properties |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4617315A (en) |
| EP (1) | EP0167426B1 (en) |
| JP (1) | JPS6110510A (en) |
| AT (1) | ATE49958T1 (en) |
| AU (1) | AU578952B2 (en) |
| CA (1) | CA1251140A (en) |
| DE (1) | DE3575716D1 (en) |
| DK (1) | DK232885A (en) |
| FR (1) | FR2564831B3 (en) |
| IE (1) | IE57994B1 (en) |
| ZA (1) | ZA853886B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0723358B2 (en) * | 1985-11-29 | 1995-03-15 | アルベール ロラン エス． アー． | Novel aroyl derivative of pyrrole |
| FR2641464B1 (en) * | 1989-01-06 | 1994-06-03 | Rolland Sa A | NOVEL PHARMACEUTICAL COMPOSITIONS EXPRESSING INHIBITORY PROPERTIES WITH RESPECT TO PHOSPHOLIPASE A2 |
| EP1768662A2 (en) | 2004-06-24 | 2007-04-04 | Novartis Vaccines and Diagnostics, Inc. | Small molecule immunopotentiators and assays for their detection |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3752826A (en) * | 1970-01-26 | 1973-08-14 | Mcneilab Inc | Aroyl substituted pyrroles |
| GB1592996A (en) * | 1977-10-10 | 1981-07-15 | Rolland Sa A | Acylated pyrrole carboxylic acids and derivatives thereof |
| AU4091178A (en) * | 1977-10-25 | 1980-04-24 | Merck & Co Inc | Substituted mercapto acid amides |
| JPS54128567A (en) * | 1978-03-28 | 1979-10-05 | Teijin Ltd | 1-substituted-4-acyl-2-pyrrolecarboxylic acid derivative |
-
1984
- 1984-05-25 FR FR8408200A patent/FR2564831B3/en not_active Expired
-
1985
- 1985-05-17 IE IE1229/85A patent/IE57994B1/en not_active IP Right Cessation
- 1985-05-22 ZA ZA853886A patent/ZA853886B/en unknown
- 1985-05-24 US US06/738,043 patent/US4617315A/en not_active Expired - Fee Related
- 1985-05-24 AU AU42882/85A patent/AU578952B2/en not_active Ceased
- 1985-05-24 EP EP85401027A patent/EP0167426B1/en not_active Expired - Lifetime
- 1985-05-24 AT AT85401027T patent/ATE49958T1/en not_active IP Right Cessation
- 1985-05-24 CA CA000482277A patent/CA1251140A/en not_active Expired
- 1985-05-24 DK DK232885A patent/DK232885A/en not_active Application Discontinuation
- 1985-05-24 JP JP60111955A patent/JPS6110510A/en active Granted
- 1985-05-24 DE DE8585401027T patent/DE3575716D1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0167426B1 (en) | 1990-01-31 |
| FR2564831B3 (en) | 1986-09-05 |
| AU578952B2 (en) | 1988-11-10 |
| EP0167426A1 (en) | 1986-01-08 |
| DK232885A (en) | 1985-11-26 |
| JPS6110510A (en) | 1986-01-18 |
| AU4288285A (en) | 1985-11-28 |
| JPH0553772B2 (en) | 1993-08-10 |
| DK232885D0 (en) | 1985-05-24 |
| CA1251140A (en) | 1989-03-14 |
| ATE49958T1 (en) | 1990-02-15 |
| FR2564831A1 (en) | 1985-11-29 |
| US4617315A (en) | 1986-10-14 |
| IE57994B1 (en) | 1993-06-02 |
| ZA853886B (en) | 1986-08-27 |
| DE3575716D1 (en) | 1990-03-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |